rs11196445

Positions:

• chr10-113710131-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001227.5(CASP7):​c.111-10901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,196 control chromosomes in the GnomAD database, including 1,094 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1094 hom., cov: 33)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

Genes affected

CASP7 (HGNC:1508): (caspase 7) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5	c.111-10901G>A		intron_variant		ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.111-10901G>A		intron_variant		1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17269 AN: 152078 Hom.: 1092 Cov.: 33

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17275 AN: 152196 Hom.: 1094 Cov.: 33 AF XY: 0.114 AC XY: 8493 AN XY: 74400

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.145

Alfa AF: 0.122 Hom.: 1241

Bravo AF: 0.110

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11196445; hg19: chr10-115469890;